Functional imaging of the human dopaminergic midbrain

Invasive recording of dopamine neurons in the substantia nigra and ventral tegmental area (SN/VTA) of behaving animals suggests a role for these neurons in reward learning and novelty processing. In humans, functional magnetic resonance imaging (fMRI) is currently the only non-invasive event-related method to measure SN/VTA activity, but it is debated to what extent fMRI enables inference about dopaminergic responses within the SN/VTA. We consider the anatomical and functional parcellation of the primate SN/VTA and find that its homogeneity suggests little variation in the regional specificity of fMRI signals for reward-related dopaminergic responses. Hence, these responses seem to be well captured by the compound fMRI signal from the SN/VTA, which seems quantitatively related to dopamine release in positron emission tomography (PET). We outline how systematic investigation of the functional parcellation of the SN/VTA in animals, new developments in fMRI analysis and combined PET–fMRI studies can narrow the gap between fMRI and dopaminergic neurotransmission.